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Category: genetics

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Inherited mutations in the gene BRCA2 significantly increase the risk of carriers to breast and ovarian cancers. BRCA2, a crucial player in the body’s DNA repair system, aids in repairing damaged DNA. This function is particularly intriguing as our cells constantly divide and replicate, passing on any genetic damage to newly developing cells.

Because of its significant role in maintaining genetic stability, BRCA2 belongs to a class of genes known as tumor suppressors. These genes code for proteins that control how often cells divide. However, when a tumor suppressor gene, such as BRCA2, undergoes a mutational change, the protein it codes for won’t function normally, resulting in uncontrolled cell division and, in some circumstances, cancer development.

BRCA2 predisposes carriers to cancer and research has shown that BRCA2-deficient tumors respond to therapies known as PARP inhibitors, which block the function of the poly ADP-ribose polymerase 1 (PARP1) protein. PARP1 becomes activated in tumors with BRCA2 mutations, resulting in the continued abnormal growth of damaged DNA.

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❤️ Check out Lambda here and sign up for their GPU Cloud: https://lambda.ai/papers.

Guide for using DeepSeek on Lambda:
https://docs.lambdalabs.com/education/large-language-models/…dium=video.

📝 AlphaEvolve: https://deepmind.google/discover/blog/alphaevolve-a-gemini-p…lgorithms/
📝 My genetic algorithm for the Mona Lisa: https://users.cg.tuwien.ac.at/zsolnai/gfx/mona_lisa_parallel_genetic_algorithm/

📝 My paper on simulations that look almost like reality is available for free here:
https://rdcu.be/cWPfD

Or this is the orig. Nature Physics link with clickable citations:
https://www.nature.com/articles/s41567-022-01788-5

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Continue reading “DeepMind’s AlphaEvolve AI: History In The Making!” | >

The development of COVID-19 vaccines has sparked widespread interest. mRNA-based therapies are rapidly gaining attention owing to their unique advantages in quickly developing vaccines and immunotherapy for various ailments [1, 2]. Given that most human diseases stem from genetic factors, gene therapy represents a promising modality for addressing various inherited or acquired disorders by replacing faulty genes or silencing genes [3]. Gene therapy encompasses the targeted exploitation of genetic material, which includes gene replacement through DNA or mRNA [4, 5]; gene silencing utilizing siRNA or miRNA [6], and CRISPR-Cas9 based gene editing [7].

However, achieving safe and efficient gene delivery to specific cells requires overcoming multiple biological barriers, including extracellular obstacles such as enzyme degradation, serum protein interactions, electrostatic repulsion of genes and cell membranes, and innate immune system, as well as intracellular obstacles such as endosomal escape, transport barriers, precise release [8]. Therefore, gene vectors require several characteristics such as high gene condensation; favorable serum stability to avoid non-specific serum protein interactions, endonuclease degradation, and renal clearance; achieved specific targeting cell or tissues; effective transport into the cytoplasm thereby facilitating gene transfection (mRNA, siRNA and miRNA); precise gene release and scheduling, and nuclear localization that enables DNA transcription. Comprehensive exploration of transfection mechanisms can aid in the development of high-performance gene vectors [9, 10].

Gene vectors generally include viral vectors and non-viral vectors. Presently, approximately 70% of clinical gene therapy trials employ viral vectors, which include retroviruses, lentiviruses, adenoviruses, and adeno-associated viruses. Due to their exceptional infectivity, virus-based vectors typically exhibit excellent gene transfection capabilities. However, the clinical safety of viral vectors has been questioned due to their propensity to stimulate immunogenic reactions and induce transgene insertion mutations. Moreover, viral vectors possess several limitations, including low gene loading capacity, inability to deliver large-sized genes, complicated preparation procedures, and the patient cannot be repeatedly administered [4]. In contrast, non-viral vectors, particularly lipid nanoparticles (LNPs) and cationic polymers, have demonstrated robust gene loading capacity, heigh safety and practicability, simplicity preparation [10, 11]. Consequently, non-viral vectors are exhibiting tremendous potential for further clinical development and application. Our review primarily highlights the significant potential of non-viral vectors, particularly lipid nanoparticles (LNPs), highly branched poly(β-amino ester) (HPAE), single-chain cyclic polymer (SCKP), poly(amidoamine) (PAMAM) dendrimers, and polyethyleneimine (PEI). We intend to provide a detailed examination of the latest research progress and existing limitations of non-viral gene vectors over recent years.

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Irritable bowel syndrome (IBS) is a prevalent and debilitating gastrointestinal disorder affecting approximately 5%–10% of the global population. Characterized by abdominal pain, bloating, and altered bowel habits, IBS imposes a significant burden on quality of life and health care systems worldwide.

Despite its prevalence, the exact pathogenesis of IBS remains elusive, and effective prevention strategies are lacking. Di Liu and colleagues conducted a comprehensive Mendelian randomization (MR) study—an approach that uses genetic variants as instrumental variables to infer causality.

The study integrates Mendelian randomization (MR) and multiresponse MR (MR2) analyses to distinguish genuine causal relationships from shared or spurious associations. The research is published in the journal eGastroenterology.

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Ask scientists which gene-editing tool is most needed to advance gene therapy, and they’d probably describe a system that’s now close to realization in the labs of Samuel Sternberg at Columbia University Vagelos College of Physicians and Surgeons and David Liu at the Broad Institute of MIT and Harvard.

The gene editor—called evoCAST—goes a long way toward solving a problem that has confounded the development of gene therapies from the field’s beginnings: How to add long stretches of DNA to defined locations in the without creating unwanted modifications.

The latest iteration of the editor, which utilizes complex enzymes found in bacteria, can be programmed to insert an entire gene—or multiple genes—into a specific location in the human genome with an efficiency suitable for gene therapy. Details of the editor are described in a paper published in Science.

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“These neurons are playing an outsized role in hyperglycemia and type 2 diabetes,” said UW Medicine endocrinologist Dr. Michael Schwartz, corresponding author of the paper.

To determine if these neurons contribute to elevated blood sugar in diabetic mice, researchers employed a widely used viral genetics approach to make AgRP neurons express tetanus toxin, which prevents the neurons from communicating with other neurons.

Unexpectedly, this intervention normalized high blood sugar for months, despite having no effect on body weight or food consumption.

Conventional wisdom is that diabetes, particularly type 2 diabetes, stems from a combination of genetic predisposition and lifestyle factors, including obesity, lack of physical activity and poor diet. This mix of factors leads to insulin resistance or insufficient insulin production.

Until now, scientists have traditionally thought the brain doesn’t play a role in type 2 diabetes, according to Schwartz.

The paper challenges this and is a “departure from the conventional wisdom of what causes diabetes,” he said.

The new findings align with studies published by the same scientists showing that injection of a peptide called FGF1 directly into the brain also causes diabetes remission in mice. This effect was subsequently shown to involve sustained inhibition of AgRP neurons.

Continue reading “Abstract: For several years, researchers have known that hyperactivity of a subset of neurons located in the hypothalamus, called AgRP neurons, is common in mice with diabetes” | >